U.S. patent application number 13/579381 was filed with the patent office on 2013-02-28 for oral smokeless tobacco products and oral smokeless non-tobacco snuff products comprising carbamide or carbamide salts.
This patent application is currently assigned to SWEDISH MATCH NORTH EUROPE AB. The applicant listed for this patent is Dowen Birkhed, Herman Norstrom. Invention is credited to Dowen Birkhed, Herman Norstrom.
Application Number | 20130053603 13/579381 |
Document ID | / |
Family ID | 44483188 |
Filed Date | 2013-02-28 |
United States Patent
Application |
20130053603 |
Kind Code |
A1 |
Norstrom; Herman ; et
al. |
February 28, 2013 |
ORAL SMOKELESS TOBACCO PRODUCTS AND ORAL SMOKELESS NON-TOBACCO
SNUFF PRODUCTS COMPRISING CARBAMIDE OR CARBAMIDE SALTS
Abstract
Oral smokeless tobacco products and oral smokeless non-tobacco
snuff products include carbamide or carbamide salt(s). The
carbamide salt is chosen from the group including carbamide calcium
sulphate [4(CH.sub.4N.sub.2O).CaSO.sub.4], carbamide magnesium
sulphate [6(CH.sub.4N.sub.2O).MgSO.sub.4.2H.sub.2O] and carbamide
sodium chloride [CH.sub.4N.sub.2O).NaCl.H.sub.2O]. Moreover,
carbamide or carbamide salt(s) are used in the manufacturing of
oral smokeless tobacco products or oral smokeless non-tobacco snuff
products.
Inventors: |
Norstrom; Herman; (Goteborg,
SE) ; Birkhed; Dowen; (Goteborg, SE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Norstrom; Herman
Birkhed; Dowen |
Goteborg
Goteborg |
|
SE
SE |
|
|
Assignee: |
SWEDISH MATCH NORTH EUROPE
AB
Stockholm
SE
|
Family ID: |
44483188 |
Appl. No.: |
13/579381 |
Filed: |
February 15, 2011 |
PCT Filed: |
February 15, 2011 |
PCT NO: |
PCT/SE2011/050162 |
371 Date: |
November 5, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61305432 |
Feb 17, 2010 |
|
|
|
Current U.S.
Class: |
564/63 |
Current CPC
Class: |
A24B 15/30 20130101;
A24B 13/00 20130101; A24B 15/16 20130101; A24B 15/287 20130101 |
Class at
Publication: |
564/63 |
International
Class: |
C07C 275/02 20060101
C07C275/02 |
Foreign Application Data
Date |
Code |
Application Number |
Feb 17, 2010 |
SE |
1000154-3 |
Claims
1. An oral smokeless tobacco product or an oral smokeless
non-tobacco snuff product, comprising carbamide or a carbamide
salt.
2. A product according to claim 1, wherein the carbamide salt is
chosen from the group comprising carbamide calcium sulphate
[4(CH.sub.4N.sub.2O).CaSO.sub.4], carbamide magnesium sulphate
[6(CH.sub.4N.sub.2O).MgSO.sub.4.2H.sub.2O] and carbamide sodium
chloride [CH.sub.4N.sub.2O).NaCl.H.sub.2O].
3. A product according to claim 1, wherein the carbamide or the
carbamide portion of the carbamide salt is present in an amount of
from 0.1 mg/g to 200 mg/g of the final product.
4. A product according to claim 1, wherein the carbamide or the
carbamide portion of the carbamide salt is present in an amount of
from 0.5 to 60 mg/g of the final product.
5. A product according to claim 1, wherein the carbamide or the
carbamide portion of the carbamide salt is present in an amount of
from 2.5 to 20 mg/g of the final product.
6. A product according to claim 1, wherein the oral smokeless
tobacco product is moist snuff such as snus, or chewing tobacco,
oral dry snuff or hard snuff.
7. A product according to claim 1, wherein the oral smokeless
non-tobacco snuff product is shaped into a form resembling moist
snuff such as snus, or chewing tobacco, oral dry snuff or hard
snuff.
8. Method of using carbamide or a carbamide salt in the
manufacturing of an oral smokeless tobacco product or an oral
smokeless non-tobacco snuff product, which comprises adding an
effective amount thereof to a product mixture used in the
manufacture of an oral smokeless tobacco product or an oral
smokeless non-tobacco snuff product.
9. A product according to claim 2, wherein the carbamide or the
carbamide portion of the carbamide salt is present in an amount of
from 0.1 mg/g to 200 mg/g of the final product.
10. A product according to claim 2, wherein the carbamide or the
carbamide portion of the carbamide salt is present in an amount of
from 0.5 to 60 mg/g of the final product.
11. A product according to claim 2, wherein the carbamide or the
carbamide portion of the carbamide salt is present in an amount of
from 2.5 to 20 mg/g of the final product.
12. A product according to claim 2, wherein the oral smokeless
tobacco product is moist snuff such as snus, or chewing tobacco,
oral dry snuff or hard snuff.
13. A product according to claim 2, wherein the oral smokeless
non-tobacco snuff product is shaped into a form resembling moist
snuff such as snus, or chewing tobacco, oral dry snuff or hard
snuff.
Description
FIELD OF INVENTION
[0001] The present invention relates to oral smokeless tobacco
products and oral smokeless non-tobacco snuff products comprising
carbamide.
BACKGROUND
[0002] Certain groups of facultative anaerobic microorganisms
present on the surfaces of the tooth, called dental plaque, present
in the form of a bio-film, are capable of metabolizing (fermenting)
carbohydrates into organic acids, especially lactic acid. As a
consequence, plaque-pH is lowered from 6.5-6.7 down to pH 4-5. At a
pH of 6.0-6.2, the dentine of the tooth starts to degrade in a
process known as "demineralization", where calcium and phosphate
ions dissolve. Below a critical pH of 5.5-5.7, the enamel
demineralises. When the acidity is neutralized to normal pH of
6.5-6.7 in the oral cavity, calcium and phosphate ions in the
saliva are precipitating on the tooth surfaces. At supersaturation
of the ions, the degraded areas are regenerated in a
"remineralization" process. If the demineralization is too advanced
for a successful remineralization to be obtained, caries lesions
will occur. Consequently, frequent exposure to carbohydrates,
resulting in a low pH in the oral cavity, may with time cause
caries lesions. It is well known that the caries risk is lower if
demineralization is avoided or if remineralization is
stimulated.
[0003] Oral smokeless tobacco products are used in the oral cavity
in direct contact with oral mucosa, where they are allowed to
deliver flavor(s) and biologically active substances. The products
are used in the mouth for an extended period of time, normally
between 10 and 60 minutes and sometimes even longer. Typical oral
smokeless tobacco products are for example moist snuff such as
snus, and chewing tobacco, hard snuff and oral dry snuff.
[0004] Oral smokeless non-tobacco snuff products are products
resembling oral smokeless tobacco products and are used in the same
way as oral smokeless tobacco products.
[0005] Most oral smokeless tobacco products, as well as oral
smokeless non-tobacco snuff products, contain carbohydrates.
Tobacco naturally contains sugars and curing of the tobacco
increases the sugar content as polysaccharides are broken down to
sugar (mono- and disaccharides). Oral smokeless non-tobacco snuff
products are usually based on plant materials which normally
contain carbohydrates, such as sugars and starch. Oral smokeless
tobacco products, as well as oral smokeless non-tobacco snuff
products, may also have carbohydrates added to the raw material in
the manufacturing process for improving the taste and/or texture of
the product.
[0006] Generally, use of oral smokeless tobacco products as well as
oral non tobacco snuff products, with high carbohydrate content,
either naturally or by way of additives, and/or a low pH and/or a
low buffer capacity, increases the risk of demineralization of the
teeth.
[0007] It is known that repeated use of oral smokeless tobacco
products as well as oral smokeless non-tobacco snuff products could
cause gingival retraction and exposure of the root surface of
teeth, likely as a consequence of mechanical stress. Since root
surfaces are not covered by enamel, such surfaces are more prone to
acid attacks of the dentine. As oral smokeless tobacco products as
well as oral smokeless non-tobacco snuff products are used close to
the teeth surfaces, it is of importance to prevent the teeth from
demineralization possible to arise as a result of bacterial
fermentation of carbohydrates originating from the products
themselves, or other carbohydrates present in the oral cavity,
during use of the products.
[0008] Hence, there exists a need for oral smokeless tobacco
products and oral smokeless non-tobacco snuff products with an
improved ability to counter-act demineralization of the teeth
and/or the advent of caries lesions.
DESCRIPTION OF THE INVENTION
[0009] The present invention provides an oral smokeless tobacco
product or an oral smokeless non-tobacco snuff product (herein
below also referred to as the "product") by which the
above-mentioned problems may be overcome. The oral smokeless
tobacco product or the oral smokeless non-tobacco snuff product is
defined in the appended claims. The product has caries-preventive
properties. The product comprises carbamide, also known as "urea",
and/or, carbamide salt(s). Examples of carbamide salts are
carbamide calcium sulphate [4(CH.sub.4N.sub.2O).CaSO.sub.4],
carbamide magnesium sulphate
[6(CH.sub.4N.sub.2O).MgSO.sub.4.2H.sub.2O] and carbamide sodium
chloride [CH.sub.4N.sub.2O).NaCl.H.sub.2O]. When not using pure
carbamide for manufacturing of the product, but carbamide salts,
the amount of the respective carbamide salt is advantageously
chosen so that the equivalent amount of carbamide is released as
would be released from the product if only neat carbamide was used.
For the combination of carbamide and/or one or more salts thereof,
an amount of each compound is added to the product so that the
total level of carbamide desired to be available for release from
the product is reached. Said group of carbamide and salts thereof
is herein below collectively referred to as "carbamide", unless
specifically defined otherwise.
[0010] Carbamide naturally occurs in small amounts in saliva and
the bacterial constitutive enzyme urease hydrolyses it into
ammonium carbonate and further into ammonia and carbon dioxide:
[(NH.sub.2).sub.2CO+2H.sub.2O.fwdarw.(NH.sub.4).sub.2CO.sub.3.fwdarw.2NH.-
sub.3+H.sub.2O+CO.sub.2]. The ammonia instantaneously reacts with
any present acid, whereby teeth plaque-pH is increased. Ureolytic
bacteria (i.e. bacteria capable of hydrolysing carbamide) are
commonly found in the mouth and ureolytic activity has been
demonstrated in saliva as well as in dental plaque. However, it has
been shown that normal levels of acid in dental plaque from
anaerobic decomposing of carbohydrates, is not totally inhibited by
urea at concentrations likely to naturally occur in the oral
cavity.
[0011] In accordance with the invention, an oral smokeless tobacco
product or an oral smokeless non-tobacco snuff product releasing
carbamide in the oral cavity is provided. Carbamide may be
incorporated in the matrix of the product, for example in the
tobacco or non-tobacco plant material mixture of the product. The
oral use of the product, normally between gum and lip, implies that
the matrix slowly will be soaked by the saliva. Subsequently
carbamide, which is highly soluble, will be released into the oral
cavity. Thus, carbamide will gradually leave the product to be
transported to the dental plaque by saliva passing through the
products' matrix. The concentration of carbamide will be the
highest in areas close to where the product is placed, but the
natural flow of saliva in the oral cavity will provide also distant
dental sites with carbamide. Entering the outer layers of plaque,
carbamide will instantaneously be broken down to carbon dioxide and
ammonia by the bacterial enzyme urease. The ammonia will react with
any present acid, whereby the plaque-pH is neutralized and even
increases for the period of time the product is used. Hence, a
carbamide releasing product with plaque-pH neutralizing properties
is provided.
[0012] The long lasting tooth-protection, obtained in accordance
with the current invention, ensures a plaque-pH neutralizing effect
during the entire period of time the products are used in the
mouth, or a substantial part thereof. The described effect not only
protects the teeth from demineralization possibly caused by the
oral smokeless tobacco product or the oral smokeless non-tobacco
snuff product itself. The slow release of carbamide and the
distribution of carbamide to distant sites in the oral cavity by
the natural flow of saliva, also underlie the long-lasting
caries-preventive properties of the products. Hence, for example
oral smokeless non-tobacco snuff products with carbamide as an
active ingredient, could be used for the purpose of protecting
teeth from demineralization and caries lesions after e.g. the
intake of a meal.
[0013] For products of the invention the long-term plaque-pH
neutralizing effect and long-term elevation of plaque-pH has been
confirmed in our in vivo studies of carbamide. Results show not
only the rapid plaque-pH elevation effect of carbamide, but also
that the delivery system in the shape of an oral smokeless tobacco
product or an oral smokeless non-tobacco snuff product, provides
the advantageous slow release of carbamide. The slow release of
carbamide secures the delivery of carbamide to the plaque surfaces
during the entire period of time the product is used in the mouth,
and provides the long-lasting plaque-pH neutralization. In vivo
studies have also shown that oral smokeless tobacco products and
oral smokeless non-tobacco snuff products containing carbamide
provide caries preventive effect not only directed to the dental
sites close to where the product is placed but to a certain extent
throughout the entire oral cavity. Typically, use of a 1 g oral
smokeless non-tobacco product comprising 1% of carbamide for 60
minutes, has shown an increase in plaque-pH from 6.7 to 7.2 close
to the oral site where the product is placed and from 6.7 to 7.0 in
an oral site opposite the site where the product is placed.
Consequently, the rapid, long-term and extensive plaque-pH
neutralizing effect during use of oral smokeless tobacco products
or oral smokeless non-tobacco snuff products with carbamide, proves
the considerable advantage of incorporating carbamide to any oral
smokeless tobacco products or oral smokeless non-tobacco snuff
products with carbohydrates and/or a neutral or near-neutral pH
and/or an absent or low pH buffering capacity. For the products
comprising carbamide, the teeth will be protected from caries
lesions possible to be caused by the products themselves.
Furthermore, the important protection against demineralization of
the dentine in exposed root surfaces and enamel will be
provided.
[0014] A number of oral smokeless tobacco products may have a
higher buffer capacity due to the nicotine content in the tobacco
and may also have an alkaline pH. The latter may be typical for
e.g. snus products. The buffer capacity and the alkaline pH of e.g.
snus may compensate to a large extent for drop in pH in the oral
cavity during use, which contributes of course to counteraction of
demineralization of the teeth. However, addition of carbamide
according to the invention into these products may further improve
their ability of improving oral health, i.e., protection against
demineralization and carries lesions, especially in connection with
intake of e.g. a meal rich in carbohydrates.
[0015] The plaque-pH neutralizing properties brought by the slow
release of carbamide during oral use of products of the invention,
shows that there is an increase in pH close to the oral site where
the product is placed. For oral smokeless tobacco products with
carbamide, the elevated pH around the product will further force
charged nicotine ions released from the tobacco to their unionized
state. Hence, in accordance with the invention, there is provided
an increase of the amount of nicotine available for absorption
through the mucous membrane.
[0016] Carbamide-containing oral smokeless non-tobacco snuff
products may also be used with the direct intention of them
preventing demineralization and caries lesions of teeth. The
purpose of the product is then two-fold: firstly to prevent the
demineralization possibly caused by use of the product if the
product is rich in carbohydrates and/or has a neutral or
near-neutral pH and/or has an absent or low pH buffering capacity,
and secondly to support neutralization of acids formed as a result
of fermentation of carbohydrates originating from intake of e.g.
food or drinks.
[0017] The content of carbamide, or the carbamide portion of the
carbamide salt(s), as the case may be, of the final product,
available for release in the oral cavity, may be in an amount of
from 0.01% by weight (0.1 mg/g) to 20.0% by weight (200 mg/g),
calculated as carbamide on total weight of the final product. Final
product is herein used as meaning the finished product in condition
to be packaged and marketed, having a moisture content
characteristic of the respective product. The total weight of the
final product is the sum of all dry and moist substances in the
final product. The amount of carbamide may in an alternative
embodiment be in the range of from 0.05% by weight (0.5 mg/g) to 6%
by weight (60 mg/g), for example from 0.25% by weight (2.5 mg/g) to
2% by weight (20 mg/g), as calculated on total weight of the final
product.
[0018] Any known type of oral smokeless tobacco or oral non-tobacco
snuff product may be used in accordance with the invention. The
products may be shaped into any suitable form and packaged in any
desirable type of packaging.
[0019] The oral smokeless tobacco product may be e.g. moist snuff
such as snus, or chewing tobacco, oral dry snuff or hard snuff. The
oral smokeless non-tobacco snuff product may be shaped into a form
resembling e.g. moist snuff such as snus, or chewing tobacco, oral
dry snuff or hard snuff.
[0020] The moist snuff such as snus, or oral dry snuff, or
alternatively the oral smokeless non-tobacco product shaped into a
form resembling moist snuff such as snus, or oral dry snuff, may be
in loose, particulate form or pre-packed.
[0021] The chewing tobacco, or alternatively the oral smokeless
non-tobacco product shaped into a form resembling chewing tobacco,
may be in loose-leaf form, in the form of a plug, roll or twist, or
as cut pieces of a strand.
[0022] The hard snuff, or alternatively the oral smokeless
non-tobacco product shaped into a form resembling hard snuff, may
be in the form of a film, strip, pellet, pod, cake, stick, tablet
or lozenge.
[0023] The oral smokeless tobacco product or oral smokeless
non-tobacco snuff product may be packaged in a box, can, canister,
cardboard box, bag, stick-pack wrapping, plastic wrapping, paper
wrapping, foil wrapping, blisterpack or on a tray.
[0024] According to the present invention, there is also provided
use of carbamide or carbamide salt(s), in the manufacturing of an
oral smokeless tobacco product or an oral smokeless non-tobacco
snuff product with caries-preventive properties.
[0025] Manufacturing processes of oral smokeless tobacco products,
e.g. moist snuff such as snus, and chewing tobacco, are well known
to the person skilled in the art, and any known process thereof may
be used. Moist snuff is known as either Swedish-type snus or
American-type moist snuff.
[0026] A general description of snus manufacturing is presented by
e.g. ESTOC, European Smokeless Tobacco Council, and the GothiaTek
quality standard for snus. Methods for the manufacture of American
type moist snuff and chewing tobacco are described in e.g.
`Wahlberg, I., Ringberger, T. (1999) Smokeless Tobacco. In:
Tobacco: Production, Chemistry and Technology, (eds D. L. Davis
& M. T. Nielsen) pp. 452-460. World Agriculture Series,
Blackwell Science Ltd. Tobacco is the raw material in any oral
smokeless tobacco product. However, for the reason of controlling
the nicotine content of the products, the raw material may well be
constituted of a mixture of tobacco and other plant materials.
[0027] The principle of snus manufacturing is to mix ground or cut
tobacco with water and sodium chloride and heat treating the
mixture for a period of time long enough (typically several hours),
and at a temperature high enough, to meet the demands for
pasteurization. The heat treatment also gives texture and color to
the mixture and enhances the natural tobacco flavors. After heat
treatment the mixture is chilled. Additives such as pH-regulators
and flavourings are then added and the mixture may be adjusted in
moisture content. The ready-made blend is packed, typically in
boxes as loose snus or as portions (pouches or sachets). Snus is
typically used between the upper gum and lip and is well known as
the Swedish-type of oral smokeless tobacco.
[0028] American-type moist snuff is commonly produced through a
fermentation process of moisturized ground or cut tobacco. Flavors
and ingredients are mixed to the blend and water is added to adjust
the moisture content. American-type moist snuff is available in a
loose form or as pre-packed pouches and is most commonly used
between the lower gum and lip but could also be used as snus
between the upper gum and lip.
[0029] Chewing tobacco is most often made of loose leaf tobacco,
which is cured at a slightly elevated temperature. The tobacco
leaves are then threshed into flakes and the mid-rids (stems) are
removed. The tobacco fragments thus obtained are usually treated
with a solution of flavors and additives, dried to lower the
moisture content and packed in a consumer package. The product
achieved is known as "loose-leaf chewing tobacco". The treated
tobacco fragments could also be compressed to blocks of tobacco
(product known as "plugs") or spun to thick strands of tobacco
(product known as "twist"). For the Scandinavian type of chewing
tobacco, the strands are thinner and cut into pieces. Chewing
tobacco is normally used by putting a pinch of the loose leaf
chewing tobacco or a bite of the plug or twist in the lower part of
the mouth between the lower gum and lip. Scandinavian chewing
tobacco, i.e. pieces of a strand, is normally used in the same way
as snus. By chewing the tobacco once in a while, flavor is released
more efficiently. Chewing tobacco as referred to here is the
typical kind of chewing tobacco used in North America, commonly
known as "chew" or "chaw", or Scandinavian chewing tobacco.
[0030] Hard snuff is a group of oral tobacco-based products
intended for oral use as a delivery system of nicotine from
tobacco. Besides the additive carrying the active substance, which
is tobacco carrying nicotine, hard snuff products are generally
constituted by entirely or substantially inert materials such as
fibres and polymers. They may also be mainly constituted by
powdered tobacco. Examples of hard snuff products are products in
the shape of a film, strip, lozenge or tablet.
[0031] Dry oral snuff resembles snus and American-type moist snuff
but is characterized by being made of a finely ground tobacco
powder and having a low moisture content (typically less than 10%).
The product may be heat treated but is normally manufactured from
fire-cured fermented tobacco which is ground into a powder to which
other ingredients such as flavors are added.
[0032] Manufacturing of oral smokeless non-tobacco snuff products
typically follows the procedure of manufacturing of oral smokeless
tobacco products, with the obvious difference that tobacco is
replaced by non tobacco raw material, typically constituted of
non-tobacco plant materials. Suitable plant materials are
non-tobacco fibres, preferably characterized by having high dietary
fibre content. Examples of such materials are oat fibres (dietary
fibre content >85%), apple fibres (dietary fibre content approx.
50-60%), sugar beet fibres (dietary fibre content approx. 65-75%),
potato fibres (dietary fibre content approx. 70%), corn fibres
(dietary fibre content approx. 70-80%), buckwheat fibres (dietary
fibre content approx. 90%), cocoa fibres (dietary fibre content
approx. 50%), cellulose fibres (dietary fibre approx. 95-99%). Oral
smokeless non-tobacco snuff products are used in the same manner as
the corresponding oral smokeless tobacco products. They offer a
healthier alternative to oral smokeless tobacco products, since
they do not contain tobacco and most often do not contain any
nicotine. In accordance with the invention, oral smokeless
non-tobacco snuff products may also be used for the administration
of drugs, as delivery systems intended for oral use and controlled
release of biologically active substances.
[0033] To produce the oral smokeless tobacco product or oral
smokeless non-tobacco snuff product according to the invention,
carbamide may be added to the product mixture in any of the process
steps of the manufacturing process. Carbamide may be added in its
normal state as a white crystalline solid or as an aqueous
solution. Preferably carbamide is added after the heat treatment or
fermentation for the possibility to calculate the exact amount of
carbamide to add to reach the desired content of carbamide in the
final product. Care is taken to ensure that carbamide is not
decomposed due to excessive heat. The person skilled in the art
would realize at what process steps carbamide is most suitably
added to the mixture. After addition of carbamide, the tobacco or
non-tobacco blend must be mixed enough to have the carbamide
homogeneously distributed in the blend.
[0034] The carbamide may also be added to the product in any other
suitable manner of incorporating additives into smokeless products
being known in the art.
[0035] The carbamide-containing blend may be packed in loose,
particulate form, loose-leaf form, in the form of a pre-packed
portion such as a pouch or sachet, in the form of a pellet, pod,
cake, film, strip, tablet, lozenge or stick, as pieces of a strand
or in the form of a plug or twist. The ready-made product may be
packed in a consumer package such as a box, can, canister,
cardboard box, bag, stick-pack wrapping, plastic wrapping, paper
wrapping, foil wrapping, blisterpack or on a tray.
[0036] The present invention shall now be described with reference
to accompanying figures and examples. The embodiments shall merely
be seen as an illustration of the spirit and scope of the current
invention, and in no way whatsoever as a limitation.
SHORT DESCRIPTION OF THE FIGURES
[0037] FIG. 1: Chart of permanent teeth with numbering according to
the FDI two-digit system. Site 12/13 is marked as the site where
plaque-pH is measured in Example 1-4. Site 15/16 and 44/45 are
marked as the two additional sites for plaque-pH measurement in
Example 4. The schematic pouch seen close to site 12/13 marks the
upper jaw position where oral smokeless tobacco products and oral
smokeless non-tobacco snuff products commonly are placed under the
lip.
[0038] FIG. 2: Graph of plaque-pH in the anterior teeth in the
upper jaw (site 12/13) during the use of portion-packed snus
products placed under the lip. Products tested were one reference
product (Low nic.#1) and two products with carbamide as an active
ingredient; 0.5% (Low nic.#2) and 1.5% (Low nic.#3). pH at each
time point (1, 3, 5, 10, 15, 20, 45 and 60 min) represents the
average of three subjects.
[0039] FIG. 3: Graph of plaque-pH in the anterior teeth in the
upper jaw (site 12/13) during the use of pellet-formed loose-leaf
chewing tobacco products placed under the lip. Products tested were
one reference product (Chaw#1) and one product with carbamide as an
active ingredient; 0.5% (Chaw#2). pH at each time point (1, 3, 5,
10, 15, 20, 45 and 60 min) represents the average of three
subjects.
[0040] FIG. 4: Graph of plaque-pH in the anterior teeth in the
upper jaw (site 12/13) during the use of portion-packed oral
smokeless non-tobacco products placed under the lip. Products
tested were one reference product (Non-tob.#1) and two products
with carbamide as an active ingredient; 0.25% (Non-tob.#2) and 1%
(Non-tob.#3). pH at each time point (1, 3, 5, 10, 15, 20, 45 and 60
min) represents the average of ten subjects.
[0041] FIG. 5: Graph of plaque-pH in site 12/13, site 15/16 and
site 44/45 during the use of portion-packed oral smokeless
non-tobacco products placed under the lip. Products tested were one
reference product (Non-tob. Spread. #1) and one product with 1%
carbamide as an active ingredient (Non-tob. Spread. #2). The pH at
each time point (1, 3, 5, 10, 15, 20, 45 and 60 min) represents the
average of ten subjects.
METHOD
[0042] In order to prove the long-term effect of neutralization of
acids and increase in plaque-pH during oral use of oral smokeless
tobacco products and oral non-tobacco snuff products, a series of
clinical tests have been carried out at Department of Cariology,
University of Gothenburg. These tests involve use of a product
according to the invention in the oral cavity, and simultaneous
measuring plaque-pH in vivo with the MicroTouch method (Lingstrom
et al. 1993). Adult subjects, with normal salivary secretion rate
and buffer capacity, were recruited. They were asked to refrain
from tooth brushing for 3 days before the test, to assure enough
plaque on the tooth surfaces. The subjects were not allowed to eat
or drink, or to use oral smokeless tobacco products or oral
smokeless non-tobacco snuff products, within one hour before the
test.
[0043] Plaque-pH was registered by inserting an iridium
micro-electrode (Beetrode.RTM. MEPH-1; W. P. Instruments, New
Haven, Conn., USA) at various approximal dental sites. The
approximal region, which is the surface of a tooth facing the
adjacent tooth, is of special interest from a cariological point of
view since it is a region were many individuals develop caries. For
each subject, the same sites were used throughout the whole study,
i.e. site 12/13 in the upper front region, close to where the
product was placed, in all tests (Example 1-4), and sites 15/16 and
44/45 (additional sites in Example 4). The electrode was connected
to an Orion SA 720 pH/ISE Meter (Orion Research, Boston, Mass.,
USA), equipped with a porous glass reference electrode (MERE 1;
W.P. Instruments). A salt bridge was created in a 3 M KCl solution
between the reference electrode and one of the subject's fingers.
After measuring resting pH (0 min), the product was placed under
the lip in the upper jaw close to site 12/13, which is a common way
to use oral smokeless tobacco products and oral smokeless
non-tobacco snuff products. Plaque-pH was then measured at eight
different time points (1, 3, 5, 10, 15, 20, 45 and 60 min), while
the product was kept in place during the whole 60-min test period.
The subject was sitting in a dental chair and was not allowed to
talk during the test.
EXAMPLES
Example 1
A Portion-Packed Low Nicotine Snus Product with Carbamide as a
Biologically Active Ingredient
[0044] A low nicotine snus-material was manufactured in accordance
with the GothiaTek standard. It was a mixture of ground tobacco,
sugar beet fibre, sodium chloride and water, which had been
heat-treated at a temperature of 80.degree. C. for 16 hours. After
the heat-treatment, sodium carbonate was added to adjust the
mixture to an alkaline pH and the mixture was then chilled to
17.degree. C. Additional components were added to the chilled
blend; calcium carbonate and sodium carbonate for pH adjustment,
flavourings for a pleasant aroma and taste, water for moisture
adjustment and carbamide as an active substance. Carbamide
(CH.sub.4N.sub.2O, CAS#57-13-6, Sigma-Aldrich puriss grade
99.0-100.5%) was used in its solid state. As all ingredients were
added, the blend was mixed to a homogenous mixture. Two blends were
prepared with different carbamide content; one reference without
carbamide was used. The total moisture content of the blends was
around 30%.
[0045] The snus-blends were packed to portions using a standard
stick-pack machine. A standard cellulose based non-woven fabric for
snus was used as cover. The filled and sealed portions were sprayed
with an aqueous solution of propylene glycol to have a final
product of 1-g portions with a total moisture content of 50%. By
the different additions of carbamide to the blends, the three final
samples had carbamide content as shown in Table 1.
TABLE-US-00001 TABLE 1 Carbamide content in portion-packed low
nicotine snus, used in the intra-oral plaque-pH test according to
Example 1. Portion Total moisture Carbamide weight content
Carbamide (w/w of final (g) (w/w) (mg/portion) product) Low
nicotine 1 50% -- -- #1 (reference) Low nicotine 1 50% 5 0.5% #2
Low nicotine 1 50% 15 1.5% #3
[0046] The three samples were tested according to the plaque-pH
method described in the Method section. Three adult subjects were
recruited. Samples were placed under the lip in the upper jaw (site
12/13) and plaque-pH was measured in situ at eight different time
points (1, 3, 5, 10, 15, 20, 45 and 60 min). The samples were kept
in place during the entire 60-min test period. The graphs (FIG. 2)
represent the average pH value of the three subjects for each time
point.
Results
[0047] The graphs in FIG. 2 show the difference in plaque-pH
between the reference sample without carbamide (Low nic.#1) and the
two samples containing carbamide as an active ingredient; 0.5% (Low
nic.#2) and 1.5% (Low nic.#3). Carbamide increases the speed of the
initial rise in pH and moreover keeps the pH at a higher level
throughout the whole 60-min period. The higher speed of initial pH
and the higher pH during the entire test period for Low nic.#3
compared to Low nic.#2, indicates that there is a clear
dose-response between pH and the amount of carbamide added. The
lower curve shows pH of the reference sample without carbamide (Low
nic.#1). It results in an initial increase of pH and that pH is
kept at a high level (pH.about.7). Even though an oral smokeless
tobacco product, when composed as the reference, would not cause a
low pH in the oral cavity, and thus not constitute a caries risk
for persons with normal oral hygiene, the higher pH from the
samples containing carbamide proves that carbamide added to
portion-packed low nicotine oral smokeless tobacco products gives a
long-term protective effect against dental caries, which is
especially beneficial for users with poor oral hygiene.
Example 2
Loose-Leaf Chewing Tobacco with Carbamide as a Biologically Active
Ingredient
[0048] In a chewing tobacco manufacturing process, a loose leaf
chewing tobacco product was gathered prior to packing. It was split
into two parts, of which one was kept as a reference (no carbamide
added). A 10% (w/v) aqueous solution of carbamide (Sigma-Aldrich,
ACS Grade, 99.0-100.5% Purity, CAS#57-13-6, CH4N2O) was prepared.
100 ml of the solution was added to 2000 g of the loose leaf
chewing tobacco to prepare a chewing tobacco sample with 0.5% (w/w)
carbamide. After addition of the carbamide-solution, the sample was
mixed and placed in bag over night to equilibrate. Prior to
packaging, the sample was mixed again. After packaging, the
moisture content of the reference and the carbamide sample was
analysed (Table 2).
TABLE-US-00002 TABLE 2 Carbamide content in loose-leaf chewing
tobacco products used in the intra-oral plaque-pH test according to
Example 2. Test Total moisture Carbamide Carbamide ration content
(mg/test (w/w of final (g) (w/w) ration) product) Chaw#1 1 26% --
-- (reference) Chaw#2 1 26% 5 0.5%
[0049] The two samples were tested according to the
plaque-pH-method described in the Methods section. Three adult
subjects were recruited. For each sample, 1 g of the chewing
tobacco material was formed by hand to the shape of a spherical
porous pellet. The pellet was placed under the lip in the upper jaw
(site 12/13) and plaque pH was measured at eight different time
points (1, 3, 5, 10, 15, 20, 45 and 60 min). The samples were kept
in place during the entire 60-min period. FIG. 3 represents the
average pH value of the three subjects for each time point.
Results
[0050] The graphs in FIG. 3 show a decrease in plaque-pH for
chewing tobacco without carbamide (reference, Chaw#1), caused by
acid formation by fermentable carbohydrates. The pH drop was as low
as 5.4 which increases the risk for dental caries both in enamel
and dentine. The graph for Chaw#2 shows the pH-stabilizing effect
of carbamide. The plaque-pH was kept above 6.2 throughout the
period of time the product was used. These data indicates that
chewing tobacco with carbamide added to a content of 0.5%, has a
caries-preventive effect.
Example 3
A Portion-Packed Oral Smokeless Non-Tobacco Product with Carbamide
as a Biologically Active Ingredient
[0051] A non-tobacco based material was manufactured in accordance
with the GothiaTek standard. The blend was a mixture of fibres from
oat and cocoa bean, glycerol (humectant), sodium chloride and
water, which had been heat-treated at 80.degree. C. for 10 hours
and chilled to 17.degree. C. The heat treatment was carried out to
reduce natural bacteria in the fibre raw material and to bring
texture, colour, aroma and taste to the blend. Dry additives were
mixed into the blend; sodium chloride, magnesium hydroxy carbonate,
ammonium chloride and carbamide. Sodium chloride and ammonium
chloride were added as taste enhancers and to lower the water
activity of the blend. Sodium carbonate, added as an aqueous
solution, and magnesium hydroxy carbonate, were added to adjust the
blend to an alkaline pH. Carbamide (CH4N2O, CAS#57-13-6,
Sigma-Aldrich puriss grade 99.0-100.5%) was added in its solid
state. Flavourings were then added and the moisture content was
adjusted to 46% by addition of water. Moisture content was verified
by analysis. Finally, the blend was mixed to a homogenous mixture.
One reference blend was prepared without carbamide (Non-tob.#1) and
two blends were prepared with different carbamide content
(Non-tob.#2 and Non-tob.#3).
[0052] The mixed materials were packed as 1-g non-woven covered
portions using equipment for packaging of finely devided moistened
materials into individual portion packages (U.S. Pat. Specification
No. 6,135,120, "Device for packing of finely devided, moistened
tobacco material", Lofman et al.). By the different additions of
carbamide to the blends, the three final samples had carbamide
content according to Table 3.
TABLE-US-00003 TABLE 3 Carbamide content in portion-packed oral
smokeless non-tobacco products, used in the intra-oral plaque-pH
test according to Example 3. Portion Total moisture Carbamide
weight content Carbamide (w/w of final (g) (w/w) (mg/portion)
product) Non-tob. #1 1 44% -- -- (reference) Non-tob. #2 1 44% 2.5
0.25% Non-tob. #3 1 44% 10 1%
[0053] The three samples were used by ten adult subjects in the
plaque-pH-test (site 12/13). Thus, plaque-pH was measured at eight
different time points (1, 3, 5, 10, 15, 20, 45 and 60 min). Graphs
(FIG. 4) represent the average pH of the ten subjects.
Results
[0054] The lower graph in FIG. 4 shows that pH is around 6.6 for
the reference sample throughout the 60-min test period. The curves
of sample Non-tob.#2 and Non-tob.#3 show a clear increase of pH as
carbamide is present. A dose-response effect was found, i.e. more
carbamide resulted in higher pH. The steady pH at high levels for
Non-tob.#2 and Non-tob.#3 proves that carbamide is released from
the portion-packed oral smokeless non-tobacco products during the
entire 60-min period and that the long-term effect of plaque-pH
neutralization is provided.
[0055] Even though the reference sample without carbamide, which
gives a plaque-pH of 6.6, would not be of caries risk for users
with normal oral hygiene, the results prove that addition of
carbamide to oral smokeless non-tobacco products increases the
long-term effect of caries protection. The addition of carbamide is
of special interest for caries risk persons with poor oral
hygiene.
Example 4
Spreading Effect of Carbamide in the Oral Cavity
[0056] Portion-packed oral smokeless non-tobacco products were
produced according to the manufacturing process described in
Example 3. One sample was prepared as reference (Non-tob. Spread.
#1) and one sample was prepared with carbamide (Non-tob. Spread.
#2). The sample formulations are shown in Table 4.
TABLE-US-00004 TABLE 4 Carbamide content in portion-packed oral
smokeless non- tobacco products, used in the intra-oral test with
pH measurement at three different sites according to Example 4.
Portion Total moisture Carbamide weight content Carbamide (w/w of
final (g) (w/w) (mg/portion) product) Non-tob. Spread. 1 44% -- --
#1 (reference) Non-tob. Spread. 1 44% 10 1% #2
[0057] The samples were tested in the plaque-pH test according to
the described method, with ten adult subjects. pH was measured in
the upper anterior site close to where the product was placed (site
12/13), the upper posterior site 15/16 and in the lower posterior
site 44/45 (FIG. 1). The samples were kept in the same place
throughout the 60-min test period and pH was measured at eight
different time points (1, 3, 5, 10, 15, 20, 45 and 60 min). Graphs
(FIG. 5) represent the average pH of the ten subjects.
[0058] Results:
[0059] The higher plaque-pH obtained from the sample with carbamide
clearly shows the caries-preventive properties of carbamide in the
site close to where the product is placed (FIG. 5). The pH-graphs
of site 15/16 and site 44/45 prove that carbamide is spread in the
oral cavity and causes an increase in pH also in the posterior
sites. This indicates that oral smokeless tobacco or non-tobacco
products with carbamide as an active substance have
caries-preventive properties not only close to the site where the
product is placed, but also in other sites in the oral cavity.
* * * * *